Reported is a highly enantioselective copper-catalyzed Markovnikov protoboration of unactivated terminal alkenes. A variety of simple and abundant feedstock α-olefins bearing a diverse array of functional groups and heterocyclic substituents can be used as substrates, and the reaction proceeds under mild reaction conditions at ambient temperature to provide expedient access to enantioenriched alkylboronic esters in good regioselectivity and with excellent enantiocontrol. Critical to the success of the protocol was the development and application of a novel, sterically hindered N-heterocyclic carbene, (R,R,R,R)-ANIPE, as the ligand for copper.

Annulated pyridines are ubiquitous scaffolds in many bioactive molecules. A highly regio-and enantioselective Ni(0)-catalyzed endo-selective C−H cyclization of pyridines with alkenes has been developed. An unprecedented enantioselective C−H activation at pyridyl 3-or 4-positions was enabled by bulky chiral Nheterocyclic carbene ligands. This protocol provides expedient access to a series of optically active 5,6,7,8tetrahydroquinolines and 5,6,7,8-tetrahydroisoquinolines, compounds otherwise accessed with difficulty, in moderate to high yields (up to 99% yield) and enantioselectivities (up to 99% ee). To our knowledge, this is the first example of enantioselective C−H cyclization of pyridines to chiral annulated products.

Reported is ah ighly enantioselective copper-catalyzed Markovnikovp rotoboration of unactivated terminal alkenes.Avariety of simple and abundant feedstock a-olefins bearing ad iverse arrayo ff unctional groups and heterocyclic substituents can be used as substrates,a nd the reaction proceeds under mild reaction conditions at ambient temperature to provideexpedient access to enantioenriched alkylboronic esters in good regioselectivity and with excellent enantiocontrol. Critical to the success of the protocol was the development and application of an ovel, sterically hindered N-heterocyclic carbene,( R,R,R,R)-ANIPE, as the ligand for copper.The asymmetric hydro-and protoboration of alkenes has long been recognized as an important stereoselective transformation in chemical synthesis. [1] Thep reparative value of this transformation stems from its conversion of widely available alkenes into synthetically versatile enantioenriched alkyl boronates under generally mild reaction conditions.The C À Bb onds in the resulting organoboron compounds are readily transformed into ab road array of valuable products with high enantiospecificity,including those containing CÀO, CÀN, CÀC, and CÀX(X= F, Cl, Br, I) bonds. [2] However,over the past several decades and since Brownsf irst asymmetric hydroboration, [1a] and despite the considerable progress made in the development of stoichiometric [1b] and metal-catalyzed processes, [1c-e] the substrate scope of this transformation remains largely limited to styrenes, [3] alkenes bearing directing groups, [4] and electronically biased or activated alkenes. [5][6][7] Theapplication of asymmetric hydro-and protoboration to simple unactivated a-olefins abundantly found in petrochemical feedstocks has proven to be al ongstanding challenge,and even astoichiometric process remains elusive. Indeed, this class of substrates continues to pose substantial challenges for asymmetric catalysis as aw hole,w ith only ah andful of reactions developed, so far,t hat provide satisfactory levels of enantiocontrol. [8] We have recently become interested in the development of ac opper-catalyzed asymmetric protoboration of a-olefins (Figure 1a). [9] As illustrated in the proposed catalytic cycle (Figure 1b), ar egio-and enantioselective borylcupration of the terminal alkene B by the copper boryl A would afford aprimary alkylcopper intermediate D via the p-complex Ca. Abulky ligand would facilitate the selective formation of Ca by avoiding the steric interaction between the ligand and the alkene substituent as shown in Cb.Subsequent protonation of the transient alkylcopper species D with an alcohol as the proton donor would furnish the chiral protoboration product E and release the copper alkoxide F.As-metathesis reaction between F and the diboron reagent G would regenerate A and close the catalytic cycle.T he regio-and enantiocontrol of the olefin borylcupration step is the key event that determines the regio-and stereochemical outcome of the transformation. However,d espite recent advances in copper-catalyz...